Field of the Invention and Description of the Prior Art
This invention relates to an improved sustained release product and method used for administering drugs to warm blooded animals and it particularly relates to a gelatin capsule product and method for gradually releasing a drug, contained in the fill material of the capsule, to warm blooded animals; the invention more specifically relates to an improved sustained release soft elastic drug form and method of administration.
Generally speaking, orally administered drug dosage forms include elixirs or drugs administered as liquids, compressed tablets, compressed coated tablets, hard shell gelatin capsules, and soft shell gelatin capsules, all of which contain unit dosage amounts of a selected drug. The dosage regimen for drugs that are orally administered quite commonly requires a predetermined schedule of two, three or four times a day, of the unit dosage forms of the drug. It can be generally said that, with many drugs, the administration of the drug or medicament to the patient in one or two doses per day, while ensuring substantially constant blood levels with adequate drug bioavailability, is highly desirable. This is the reason for the desirability of having so-called sustained release drug dosage forms, that is, dosage forms which enable the drug to be released to the body of a warm blooded animal over an extended and generally pre-determined period of time.
Although a dosage regimen involving one or two oral doses of the drug per day is consideredto be highly desirable, not all drugs are logical candidates for a sustained release dosage form. Generally speaking, drugs having a relatively short half life, for example, less than about 8-10 hours, are good candidates for sustained release drug dosage forms. The purpose of having a sustained release dosage form for a drug is to generally flatten the plasma conconcentration curve, that is, reduce the concentration level of the drug in the plasma immediately or shortly after administration so as to attain a fairly constant plasma level for the drug. On the other hand, there is no rational basis for having sustained release preparations for drugs having a long biological half life, such as twelve hours or more. Similarly, highly potent drugs are not generally reasonable candidates for sustained release drug forms since it is desirable to have the option to withhold the drug at will during the dosage regimen so that control is not lost when the patient is under continuous medication.
Sustained release dosage forms have generally been used with hard gelatin capsules having enteric coated microcapsules therein or compressed into tablets and with coated tablets, but have generally not been used with soft gelatin capsules which are usually filled with a liquid or a flowable substance, thereby making a sustained release dosage form, as a practical matter, almost impossible. Canadian Pat. No. 888,683 relates to a sustained release soft elastic gelatin (SEG) capsule dosage form in which the capsule filling, upon coming in contact with water or with the juices of the gastrointestinal tract, forms a microporous, spongy substance, including the medicament, which gives off the active substance, continuously, through diffusion for absorption into the ambient medium.
Although the sustained release drug form disclosed in this Canadian patent does relate to a possible sustained release system used in connection with gelatin capsules, there is a need and interest in the development of sustained release formulations that are encapsulated within gelatin capsules, particularly soft elastic gelatin capsules of the type normally containing a liquid or flowable substance. Although it is not difficult to develop theoretical equations that would describe the desired release characteristics of sustained action tablets and capsules, it is another matter to formulate and manufacture products that will predictably deliver a drug under conditions which are variable due to patient physiology and therapy and yet reflect the desired plasma level profiles designed into the dosage form.